Document Type : Research Paper I Open Access I Released under CC BY-NC 4.0 license

Authors

1 Sport Physiology Student, Department of Physical Education, Boroujerd Branch, Islamic Azad University, Boroujerd, Iran

2 Assistant Professor in Sport Physiology, Department of Physical Education, Boroujerd Branch, Islamic Azad University, Boroujerd, Ira

3 Associate Professor in Sport Physiology, Department of Physical Education,Boroujerd Branch,Islamic Azad University,Boroujerd,Iran

4 Associate Professor in Sport Physiology,Sport Science Faculty,Buali Sina University,Hamadan,Iran

Abstract

Epigenetic changes and cardiac reconstruction are among the most important adaptations in endurance training. The aim of this study was to investigate the gene expression of histone deacetylase-4 and myocyte enhancer factor-2c (MEF-2c) in male rats in interaction with exhaustive swimming. 12 male Wistar rats (mean age: 7±1 weeks, weight 275±25 gr) were randomly divided into two groups (each group 6 subjects): control and training. After performing the exhaustive swimming for 3 hours per session and 5 days per week for 10 weeks, their left ventricle was isolated; then the gene expression were investigated by Real Time-PCR. Data were analyzed by independent t test and the significance level was P≤0.05. The results showed that after 10 weeks of exhaustive swimming, the HDAC4 gene significantly increased (P=0.02), but MEF-2c gene significantly decreased (P=0.001) compared with the control group. Therefore, 10 weeks of exhaustive swimming increased gene expression of HDAC-4 and consequently reduced gene expression of MEF-2c by an increase in the activity of transcription factors attached to HDAC-4.
 

Keywords

  1. Henriksen E, Sundstedt M, Hedberg P. Left ventricular end-diastolic geometrical adjustments during exercise in endurance athletes. Clin Physiol Funct Imaging 2008; 28(2): 76-80.
  2. Mihl C, Dassen WR, Kuipers H. Cardiac remodelling: concentric versus eccentric hypertrophy in strength and endurance athletes. Neth Heart J. 2008; 16 (4):129-33.
  3. Eccleston A, Cesari F, Skipper M. Transcription and epigenetics. Nature. 2013; 502 (7472): 461.
  4. Feng J, Fouse S, Fan G. Epigenetic regulation of neural gene expression and neuronal function. Pediatr Res. 2007; 61(5):58-63.
  5. Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, et al. HDAC4,  a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor. Mol Cell Biol. 1999; 19 (11):7816-27.
  6. Miska EA, Karlsson C, Langley E, Nielsen SJ, Pines J, Kouzarides T. HDAC4 deacetylase associates with and represses the MEF2 transcription factor. EMBO J. 1999; 18(18):5099-107.
  7. Nebbiso A and et al. Selective class II HDAC inhibitors impair myogenesis by modulating the stability and activity of HDAC–MEF2 complexes. EMBO reports. 2009; 10(7): 776-782.
  8. Khoshbin Nazdik M, Khazaei Koohpar Z, Sayad A. Investigation of TIMP-1 Gene Expression in Patients with Multiple Sclerosis (MS). AMUJ 2017; 20(123): 22-30.
  9. Potthoff MJ, Wu H, Arnold MA, Shelton JM, Backs J, McAnally J, et al. Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers. J Clin Invest. 2007; 117(9):2459-67.
  10. Potthoff MJ, Olson EN. MEF2: a central regulator of diverse developmental programs. Development. 2007; 134(23):4131-40.
  11. Rose AJ, Frosig C, Kiens B, Wojtaszewski JFP, Richter EA. Effect of endurance exercise training on Ca2+calmodulin-dependent protein kinase II expression and signalling in skeletal muscle of humans. J Physiol. 2007; 583(2):785-95.
  12. Backs J, Song K, Bezprozvannaya S, Chang S, Olson EN. CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy. J Clin Invest. 2006; 116(7):1853-64.
  13. Rose AJ, Frosig C, Kiens B, Wojtaszewski JFP, Richter EA. Effect of endurance exercise training on Ca2+calmodulin-dependent protein kinase II expression and signalling in skeletal muscle of humans. J Physiol. 2007; 583(2):785-95.
  14. Fathi M, Gharakanlou R, Rezaei R. The Effect of 14-Week Endurance Training on Left Ventricle HDAC4 Gene Expression of Wistar Male Rat. J Sport Biomotor Sci. 2013; 11(1): 5-15.
  15. Medeiros A, Oliveira EM, Gianolla R, Casarini DE, Negrao CE, Brum PC. Swimming training increases cardiac vagal activity and induces cardiac hypertrophy in rats. Braz J Med Biol Res. 2004; 37(12):1909-17.
  16. Obad A, Palada1 I, Valic1 Z, Ivancev V, BakovicD, 1, Wisløff U et al. The effects of acute oral antioxidants on diving-induced alterations in human cardiovascular function. J Physiol. 2007; 578(3): 859-870.
  17. Kilic M, Ulusoy O, Cirrik S, Hindistan I E, Ozkaya YG. Effect of exercise intensity on cerebrospinal fluid interleukin-6 concentration during recovery from exhaustive exercise in rats. Acta Physiol Hung. 2014; 101: 21-31.
  18. Kenneth J, Livak and Thomas D, Schmittgen. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 22-∆∆CT Method. Applied Biosystems, Foster City, California 94404; and †Department of Pharmaceutical Sciences, College of Pharmacy.
  19. DeBosch B, Treskov I, Lupu TS, Weinheimer C, Kovacs A, Courtois M, et al. Akt1 is required for physiological cardiac growth. Circulation. 2006; 113(17):2097-104.
  20. O'Neill BT, Kim J, Wende AR, Theobald HA, Tuinei J, Buchanan J, et al. A conserved role for phosphatidylinositol 3-kinase but not Akt signaling in mitochondrial adaptations that accompany physiological cardiac hypertrophy. Cell Metab. 2007; 6 (4):294-306.
  21. Liu F, Pore N, Kim M, Voong KR, Dowling M, Maity A, et al. Regulation of histone deacetylase 4 expression by the SP family of transcription factors. Mol Biol Cell. 2006; 17(2):585-97.
  22. Van Rooij, E., N. Liu, and E.N. Olson. MicroRNAs flex their muscles. Trends in Genetics. 2008; 24(4): p. 159-166.
  23. Miska EA, Karlsson C, Langley E, Nielsen SJ, Pines J, Kouzarides T. HDAC4 deacetylase associates with and represses the MEF2 transcription factor. EMBO J. 1999; 18(18):5099-107.
  24. Fathi M, Gharakhanlou R, Rajabi H. The Effect of 14 Week of Endurance Activity on miR-1 Expression of Left Ventricle in Male Wistar Rats. J Sport Biomotor Sci. 2016; 8(1): 65-75.
  25. Soci, U.P., et al. MicroRNAs 29 are involved in the improvement of ventricular compliance promoted by aerobic exercise training in rats. Physiol Genomics. 2011; 43(11): 665-73.
  26. Han, M., J. Toli, and M. Abdellatif. MicroRNAs in the cardiovascular system. Curr Opin Cardiol. 2011; 26(3): 181-9.
  27. Wan W, Xu X, Zhao W, Garza MA, Zhang JQ. Exercise training induced myosin heavy chain isoform alteration in the infarcted heart. Appl Physiol Nutr Metab. 2014; 39(2):226-32.
  28. Schneider CD, de Oliveira AR. Oxygen free radicals and exercise: mechanisms of synthesis and adaptation to the physical training. Rev Bras Med Esporte. 2004; 10:314-8.
  29. Mimić-Oka J, Simić DV, Simić TP. Free Radicals in Cardiovascular Diseases. Facta Universitatis. 1999; 6(1):11 - 22.
  30. Luijsterburg MS, Dinant C, Lans H, Stap J, Wiernasz E, Lagerwerf S, et al. Heterochromatin protein 1 is recruited to various types of DNA damage. J Cell Biol. 2009; 185(4):577-86.
  31. Hardie DG, Carling D. The AMP-activated protein kinase--fuel gauge of the mammalian cell? European journal of biochemistry / FEBS. 1997; 246 (2):259-73.
  32. Zaha VG, Young LH. AMP-activated protein kinase regulation and biological actions in the heart. Circ Res. 2012; 111 (6):800-14.
  33. Musi N, Hirshman MF, Arad M, Xing Y, Fujii N, Pomerleau J, et al. Functional role of AMP-activated protein kinase in the heart during exercise. FEBS Lett. 2005; 579 (10):2045-50.
  34. Mihaylova MM, Vasquez DS, Ravnskjaer K, Denechaud PD, Yu RT, Alvarez JG, et al. Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis. Cell. 2011; 145 (4):607-21.
  35. Wei j, Joshi SH, Speransky S, Crowley CH, et al. Reversal of pathological cardiac hypertrophy via the MEF2-coregulator interface. JCI insight. 2017; 2(16): 1-16.
  36. Backs J, et al. The delta isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload. Proc Natl Acad Sci U S A. 2009; 106 (7):2342–2347.
  37. Frey N, Katus HA, Olson EN, Hill JA. Hypertrophy of the heart: a new therapeutic target? Circulation. 2004; 109 (13):1580–1589.